PROJECT SUMMARY The H. Lee Moffitt Cancer Center & Research Institute (MCC) continues its ambitious trajectory of innovative cancer research and translation to benefit the gulf coast region of Florida and beyond. As a free-standing 501(c)3 not-for-profit institution with the sole purpose ?to contribute to the prevention and cure of cancer,? all research funding ($71.8M), publications (2,430), and clinical research (>1,600 interventional accruals/ year) are cancer focused. Research and clinical space has expanded dramatically since the last renewal to more than 2 million square feet, and patient clinical volume places MCC among the largest Centers in the United States. MCC has benefitted from recent, ongoing annual state legislature funding of approximately $25 million, in addition to more than $39 million of annual institutional research support. The 142 MCC members span the basic, clinical, and population sciences. They are organized into five highly collaborative, multidisciplinary programs with exceptional levels of intra- (35%) and inter-programmatic (18%) publications. Under the leadership of Dr. Thomas Sellers, the third MCC Director, a Research Strategic Plan (RSP) was developed and implemented for ?Moffitt 3.0.? Four of six Associate Center Directors are new; and new leaders have been appointed in every program, with bold goals and specific aims. Two of the 13 shared resources have been significantly restructured (Chemical Biology, Molecular Genomics), and one new resource created (Collaborative Data Services) to better meet the changing needs of MCC scientists. Implementation of the strategic plan has been bolstered by substantial institutional investment, especially in basic science, immunotherapy, and clinical research infrastructure, including the recruitment of 45 new faculty members, of whom 32 are CCSG members. MCC is a leader in immunotherapy, and more than 40% of overall clinical trial accrual is to investigator-initiated studies. MCC population scientists initiated significant new efforts in cancer prevention and outcomes that include vaccines, tobacco cessation, and health disparities. This is particularly true in the unique cancer problems in the catchment area ? notably lung cancer, melanoma, and HPV- prevention. MCC's Total Cancer Care protocol, the ground-breaking research strategy to realize the promise of personalized medicine, has continued to thrive, resulting in dramatic utilization of the Tissue Core and the formation of the Oncology Research Information Exchange Network (ORIEN) that now includes eleven cancer centers across the nation, with several more poised to join the consortium this year. MCC requests funding for: five scientific programs, 13 shared resources, two clinical research components, planning and evaluation, administration, leadership, four staff investigators, and developmental funds. CCSG funds are leveraged more than 10-fold with institutional resources to maximize impact on cancer prevention, treatment, and cure in the catchment area, the state of Florida and beyond.